Multi-ethnic genome study unlocks new genetic links to health conditions Genetic Metabolites HumanHealth DiseaseInsights GeneticVariants MetaboliteAnalysis PrecisionMedicine Genomics NatureComms
By Dr. Priyom Bose, Ph.D.May 31 2023 Human health status can be determined based on the circulating metabolite levels. Although it is important to understand the genetic architecture of these metabolites, to date, they are not well understood. Considering this research gap, a recent Nature Communications study focused on performing whole-genome sequencing analysis of circulating human metabolites in a multi-ethnic population.
The majority of genetic studies based on human metabolome are based on European populations, however, only a few have considered African-American and Hispanic populations. It is important to include an ethnically diverse population as it can lead to greater genetic discovery linked to varied diseases. Even though most studies have concentrated on autosomal chromosomes, it is vital to explore X chromosomes as well as better understand the genetic architecture of metabolites.
For replication analysis, independent participants from Jackson Heart Study , FHS, TwinsUK, and Women’s Health Initiative studies were obtained, which comprised AA and individuals of European ancestry. A total of 18,085 individuals were used for replication analysis. Related StoriesMendelian Randomization exhibited a total of 13 metabolites associated with the risk of 12 phenotype outcomes, such as macular degeneration and type 2 diabetes. In addition, 16 metabolites were linked to 29 protein quantitative trait loci .
Even though pooled sample analysis is computationally efficient, the variant-set test could be intensive and costly for whole genome analysis. In the current study, gene-centric rare variant analyses among 230 metabolites were initially performed, which indicated significant common variants. These metabolites exhibited relatively high heritability, which was exploited to study the impact of rare variants on these metabolites.
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